Heterogeneity within healthy biomedical populations can degrade disease-classification performance by distorting the decision boundary between healthy and diseased cohorts. In this study, the healthy cohort is decomposed into two subtypes: borderline healthy samples, defined operationally as healthy-labeled subjects that lie closer to the diseased distribution in the learned feature space, and a representative subset termed the self-tuned Homogeneous Healthy Core (H2C), characterized by high intra-class homogeneity. Using an information-theoretic framework, it is shown that training on H2C yields a tighter classification-error bound than training on the full heterogeneous healthy cohort. To operationalize this idea, a healthy-only kernel density estimation procedure with bootstrap-stability-based self-tuning is developed and evaluated on three biomedical case studies: myocardial infarction classification on PTB-XL+, arrhythmia detection, and an institutional migraine dataset. Compared with the full-healthy baseline and simpler healthy-subset baselines, H2C consistently shows strong performance on the subset-gated evaluation view in terms of F1, precision, recall, and accuracy, with the clearest advantage under the balanced training setup. For example, under the balanced training setup and subset-gated evaluation view, H2C improves mean F1 from 0.899 to 0.952 on PTB-XL+, from 0.693 to 0.854 on Arrhythmia, and from 0.643 to 0.741 on Migraine relative to the full-healthy baseline. These results show that curating a stable healthy reference subset can improve downstream classification behavior and support the construction of smaller, higher-quality healthy reference cohorts for biomedical modeling. More broadly, H2C provides a self-tuned and classifier-agnostic strategy for healthy-cohort curation, an important but often overlooked problem in biomedical machine learning.
Meningococcal vaccination of adolescents/young adults is recommended in various countries, including the United States (US). This phase 3b, observer-blind study (NCT04318548) evaluated the safety, reactogenicity, and immunogenicity of serogroup B vaccine, 4CMenB, and quadrivalent conjugate vaccine, MenACWY-CRM, when co-administered to healthy individuals aged 16-18 y, as per US Advisory Committee on Immunization Practices recommendations. Adolescents, who had received MenACWY vaccination ≥4 y previously, were randomized (N = 940; 1:1:1) to one of three groups to assess co-administration versus 4CMenB and MenACWY-CRM administered alone. Co-primary objectives were to demonstrate the non-inferiority of antibody responses after concomitant administration to antibody responses after 4CMenB (two doses administered 2 months apart) and MenACWY-CRM (single dose), as measured by human serum bactericidal assay (hSBA). Vaccine safety and reactogenicity were assessed as another primary objective. The co-primary endpoints were met: the lower limit of 2-sided 95% confidence intervals for all between-group ratios of hSBA geometric mean titers was >0.5 for the concomitant administration group versus 4CMenB group and MenACWY-CRM group. hSBA data after two 4CMenB doses and one MenACWY-CRM dose showed comparable between-group geometric mean ratios versus baseline, and percentages of participants with 4-fold rises in titers and titers ≥lower limit of quantitation. The safety profile of 4CMenB co-administered with MenACWY-CRM was comparable with that of 4CMenB administered alone. In conclusion, 4CMenB and MenACWY-CRM co-administration was well tolerated in adolescents aged 16-18 y and immune responses were comparable versus administration of each vaccine alone, which is consistent with a previous study of co-administration in infants. Invasive meningococcal disease, caused by the bacterium Neisseria meningitidis, poses a life-threatening risk but can be prevented through vaccination. Effective vaccines are available against the most common disease-causing meningococcal serogroups, A, B, C, W, and Y. Evidence from clinical studies and immunization programs over the last decade with the 4-component meningococcal serogroup B vaccine, 4CMenB, and serogroups A, C, W, and Y vaccine, MenACWY-CRM, confirms the effectiveness of both vaccines in population age groups at higher risk of meningococcal disease, including infants and adolescents. It was previously shown that the administration of 4CMenB and MenACWY-CRM to healthy infants at the same visit induced good immune responses and was well tolerated by young children. Adolescent vaccination with 4CMenB and MenACWY-CRM is recommended in various countries, including in the United States. We conducted a study to test the safety of concomitant administration and its ability to induce immune responses in 945 healthy adolescents aged 16–18 y; 834 from the United States and 111 from Italy. We found that most reactions to the 4CMenB and MenACWY-CRM injections were mild or moderate, and were similar whether the vaccines were given together or separately, with no unexpected side effects. Co-administration to adolescents induced robust immune responses against serogroup B and serogroups A, C, W, and Y. These results support the use of concomitant meningococcal vaccinations in adolescent immunization programs.
Cigarette smoke contains numerous toxicants, including cadmium, polycyclic aromatic hydrocarbons (PAHs), tobacco-specific nitrosamines (TSNAs), and volatile organic compounds, all of which may contribute to hepato-renal injury. This study, conducted in Buea (Southwest Region, Cameroon), aimed to assess cadmium inhalation exposure from cigarette smoking as a contributing factor to altered liver and kidney function biomarkers in apparently healthy smokers, while acknowledging that combined exposure to multiple co-toxicants may potentiate organ dysfunction. A survey was used to recruit smokers and collect data on their smoking habits. Cadmium contents in the major cigarette brands selected were used to estimate the cadmium Daily Exposure (DE), Weekly Inhalational Exposure (WIE) and the percentage contribution to the Tolerable Weekly Intake (TWI) of cadmium. Serum alanine aminotransferase (ALT) activity, urea, creatinine contents, and urinary albuminuria and glucosuria were measured in blood and urine samples from smokers and nonsmokers. The 102 smokers enrolled were categorized respectively as light (37.3%; 38/102), moderate (38.2%; 39/102), and heavy (24.5%; 25/102) smokers, smoking an average number of 4.7 ± 0.5, 9.1 ± 1.5, and 19.1 ± 3.0 cigarettes/day, respectively. Cadmium levels in cigarette brands ranged from 0.72-1.08 µg Cd per gram of tobacco removed from the cigarette. Heavy smokers exceeded the permitted cadmium No Significant Risk Level (NSRL) by up to 28-fold, contributing 4-8% to the cadmium TWI. Serum ALT activity and creatinine content were significantly higher (P < 0.05) in smokers groups compared to non-smokers. Also, moderate and heavy smokers were at a significantly higher risk (relative risk 6.90-13.32; P < 0.05) of displaying abnormal elevated serum urea content, positive albuminuria and glucosuria. Our findings demonstrate that healthy active smokers are highly exposed to cadmium (and potentially to other cigarette toxicants) and are at significantly higher risk of displaying abnormally elevated levels of biochemical markers of liver and kidney function, suggesting early signs of organ damage.
Variability in 24-hour and visit-to-visit blood pressure has been reported to be predictive of adverse cardiovascular outcomes. While recent studies have employed beat-to-beat blood pressure variability (BPV) as a predictor of cardiovascular risk, the reliability of beat-to-beat BPV remains equivocal. The purpose of this study was to examine intraindividual reliability of BPV, and to compare that reliability to more widely-documented heart rate variability (HRV) in young healthy adults. Continuous heart rate (HR, electrocardiogram), beat-to-beat blood pressure (BP, finger plethysmography), and respiratory rate (pneumobelt) were recorded during 10 minutes of rest in 77 participants (38 males, 39 females; age: 23±5 yr; BMI: 25±4 kg/m2) on two occasions separated by ≥2 days (25±19 days; 2-98 days). Reliability of beat-to-beat BPV, HRV (time- and frequency-domain), and additional cardiovascular (heart rate, blood pressure) assessments were quantified as relative and absolute reliability using the intraclass correlation coefficient (ICC) and the coefficient of variation (CoV), respectively. Beat-to-beat BPV demonstrated moderate relative and good absolute reliability (10-min duration: ICC=0.601-0.684, CoV=14-16%). In contrast, relative reliability of time-domain HRV was good-to-excellent, while absolute reliability was poor-to-good (10-min duration: ICC=0.844-0.904, CoV=13-34%). Frequency-domain HRV demonstrated moderate to excellent relative reliability and poor absolute reliability (10-min duration: ICC=0.626-0.903, CoV=34-37%). In summary, the rigor and reliability of continuous BPV and HRV are different when parsed out by relative vs. absolute reliability, with relative reliability being stronger with HRV and absolute reliability being stronger with BPV. These findings suggest both caution and specificity when employing continuous BPV or HRV for CVD risk stratification purposes.
Staphylococcus aureus (S aureus) commonly causes skin infections and is abundant on the skin of patients with atopic dermatitis, where it worsens inflammation and drives skin barrier defects. Neutrophils help to control S aureus infection through their antimicrobial activity and by recruiting other immune cells; however, they can also promote S aureus skin colonization. Excessive neutrophil activity and release of neutrophil extracellular traps may impair the skin barrier and thereby promote colonization. Moreover, S aureus has evolved strategies to evade neutrophil defenses. This review explores neutrophil-skin interactions in healthy and inflamed skin and potential therapeutic strategies targeting these interactions to reduce S aureus colonization in diseases like atopic dermatitis.
We conducted an open-label study to assess the pharmacokinetics, safety, and tolerability of nacubactam-a β-lactamase inhibitor-administered alone or in combination with β-lactam antibiotic. Japanese healthy male participants received a single dose of nacubactam 2 g on Day 1, a single dose of β-lactam antibiotic (cefepime 2 g, aztreonam 2 g, meropenem 2 g, and piperacillin 4 g in Cohorts 1, 2, 3, and 4, respectively) on Day 3, and the combination of nacubactam and β-lactam antibiotic on Day 5. The study drugs were intravenously administered over 60 min. A total of 32 participants (8 in each cohort) were enrolled in the study. All participants completed the study and were included in the analysis. Exposures to nacubactam or β-lactam antibiotic (maximum plasma concentration [Cmax], area under the plasma concentration-time curve from time zero to the last quantifiable time [AUC0-t], and AUC from time zero to infinity [AUC0-∞]) were similar between the treatment periods (monotherapy vs combination therapy) in all cohorts. Coadministration of nacubactam and β-lactam antibiotic did not affect the pharmacokinetic profile of nacubactam or β-lactam antibiotic with the 90% confidence intervals for the geometric least squares mean ratios (combination therapy/monotherapy) of Cmax, AUC0-t, and AUC0-∞ contained within the equivalence range of 0.80 to 1.25 for all study drugs. Nacubactam and β-lactam antibiotics were well tolerated. All treatment emergent adverse events were mild in severity and resolved without treatment. Our results support the further clinical development of nacubactam coadministered with these β-lactam antibiotics.
The proliferation of algorithmic classification systems in healthcare raises fundamental questions about medical normativity: who determines the standards of health, and through what mechanisms are those standards constructed and enforced? This paper makes three original contributions. First, it conceptualizes algorithmic normativity as a multidimensional phenomenon operating through training data selection, loss function design, and clinical deployment contexts. Second, it forges a novel analytical link between population-level structural inequity and the undertheorised phenomenological dimension of diagnostic identity fragmentation. Third, it proposes a human-centric governance framework integrating transparency, plural normativities, and meaningful patient participation as a coherent alternative to purely technical approaches to algorithmic fairness. Drawing on medical sociology, science and technology studies, and bioethics, I argue that algorithmic systems do not simply discover pre-existing medical truths but actively construct normative frameworks that reflect and reproduce social inequities embedded in their development. The question of who decides what is healthy cannot be answered through computational means alone but requires sustained democratic engagement with the ethical, social, and political dimensions of algorithmic medicine.
Polycystic ovary syndrome (PCOS) is commonly associated with obesity and metabolic disturbances. Although gut and vaginal microbiome changes have been linked to PCOS, the independent role of body mass index in these alterations remains unclear. This study aimed to compare gut and vaginal microbiomes in women with PCOS and healthy controls, emphasizing the impact of body mass index. Seventy-five women were enrolled, including 55 with PCOS and 20 healthy controls. Participants were stratified into normal-weight (<25) and overweight (≥25) groups. Vaginal and anorectal swabs were analyzed using full-length 16S rRNA Nanopore sequencing. Microbial diversity and composition were assessed with alpha diversity indices, principal component analysis, Analysis of Composition of Microbes, PERMANOVA and Vaginal Community State Types classification. Without body mass index stratification, women with PCOS showed differences in several vaginal taxa compared with healthy controls. Within the PCOS cohort, overweight women exhibited higher vaginal alpha diversity, reduced Lactobacillus dominance, and enrichment of anaerobic taxa compared with normal-weight women with PCOS. Differences in vaginal microbial composition were also observed between healthy and PCOS women with normal body mass index. In contrast, gut microbiome alterations were limited and less consistent across analytical approaches. Vaginal community State Types analysis revealed predominance of Class IV communities in both healthy women and women with PCOS. These findings suggest that higher body mass index is associated with vaginal microbiome alterations in women with PCOS, although PCOS-related factors independent of body weight may also contribute to the observed microbial differences. Polycystic ovary syndrome is a common condition that affects hormones, fertility, and metabolism in women. Many women with this condition are also overweight, but it is not fully understood how body weight influences the bacteria living in the body. In this study, we compared bacteria present in vaginal and anorectal samples from women with and without polycystic ovary syndrome, while also considering body weight. We found that women with higher body weight had more noticeable changes in vaginal bacterial composition, including lower amounts of protective Lactobacillus bacteria and higher diversity of anaerobic bacteria. At the same time, some bacterial differences were also observed in women with polycystic ovary syndrome who had normal body weight. Changes in gut bacteria were smaller and less consistent. These findings suggest that both body weight and polycystic ovary syndrome may influence vaginal bacterial composition and should be considered in future studies of women's reproductive health.
Successfully resolving self-control conflicts requires individuals to integrate information about the hedonic value of a temptation with its impact on distant goals. Functional neuroimaging research demonstrates that cue-related activity in the brain's reward system predicts self-control failures ranging from weight gain and drug use to gambling disorders. Despite this work, it remains unclear what components of the decision-making process are associated with neural cue-reactivity. The present study integrates eye-tracking and computational modeling of food choices using the attentional Drift Diffusion Model with neural measures of food cue-reactivity in a sample of chronic dieters. Our results show that activity to tempting food cues in the nucleus accumbens and orbitofrontal cortex is associated with an attentional bias towards unhealthy food items during a food choice task. Moreover, functional and structural connectivity between the brain's reward system and a prefrontal region implicated in response inhibition, were associated with a reduction in the drift rate for unhealthy food items and with the ability to maintain healthy items in mind even when gaze is directed towards unhealthy food items. Together, these findings help elucidate the relationship between neural cue-reactivity and dietary decision-making and suggest attentional biases as one mechanism through which cue-reactivity is associated with self-control failure.
To compare the performance of one point-of-care activated clotting time (ACT) machine (Vet-Tube), one point-of-care activated partial thromboplastin time (aPTT) machine (Coagulation DX), and one bench-top ACT machine (Medtronic ACT II plus) with previously published measurements from stationary devices in whole blood from healthy horses. Prospective, observational study SETTING: University veterinary teaching hospital, from August 2023 to September 2023. Thirty healthy university-owned horses. ACT and aPTT were measured via point-of-care analyzers (ACT POC, aPTT POC) and by conventional stationary analyzers (ACT Stationary, aPTT Stationary) in non-heparinized and heparinized blood collected from healthy horses. Samples were analyzed within 30 min of collection. Moderate correlation (r = 0.5), acceptable bias, and a low intraassay coefficient of variation (<5%) were seen for the ACT stationery device and ACT POC coagulation tubes. The ACT stationery and ACT POC showed no significant difference for both non-heparinized (n = 30, p = 0.64) and heparinized samples (n = 15, p = 0.43). Strong correlation but high bias and a high intraassay coefficient of variation (>5%) were seen for the aPTT POC device, with the aPTT stationary device being within previously published ranges. The aPTT stationary chemistry analyzer and aPTT POC showed a significant difference for non-heparinized samples (n = 30, p = 0.0002) but had no significant difference for heparinized samples (n = 15, p = 0.03). The results of this study provide proof of concept for the use of low-cost POC monitoring of ACT in equine patients with coagulopathy or undergoing heparin therapy. Rigorous evaluation in patients with clinical disease is still necessary.
Cerebrovascular reactivity (CVR) reflects the ability of cerebral vessels to adapt to metabolic demands and may be impaired in multiple sclerosis (MS). Its clinical relevance in relapsing-remitting MS (RRMS), particularly in relation to disability and cognition, remains uncertain. We compared CVR, quantified by the Breath-Holding Index (BHI), between patients with RRMS and healthy controls, and examined its associations with neurological disability and cognitive performance. In this cross-sectional observational study consecutive RRMS patients and age- and sex-matched healthy controls (2:1 ratio) were enrolled. CVR to hypercapnia was assessed by transcranial Doppler using BHI. Cognitive performance was evaluated with the Brief International Cognitive Assessment for MS battery, and neurological disability with the Expanded Disability Status Scale (EDSS). Multivariable linear regression was used for adjusted analyses. Ninety patients with RRMS and 45 healthy controls were included. BHI was lower in RRMS than in controls (0.88 ± 0.13 vs. 1.13 ± 0.13), with a mean difference of - 0.256 (95% CI - 0.302 to - 0.209). Lower BHI was associated with greater disability (EDSS: ρ=-0.420; 95% CI - 0.581 to - 0.228) and worse processing speed on the Symbol Digit Modalities Test (r = 0.50; 95% CI 0.33 to 0.64). In adjusted models, lower BHI remained independently associated with higher EDSS (B = - 3.51; 95% CI - 5.82 to - 1.20) and lower SDMT performance (B = 3.69; 95% CI 2.11 to 5.26). RRMS patients exhibit reduced CVR, independently associated with disability and processing speed. Impaired CVR may represent a clinically relevant marker of disability and cognitive dysfunction in RRMS.
Introduction. Myelomeningocele (MMC) is the most severe form of neural tube defects, characterized by physical, cognitive, and social sequelae. Despite advances in treatment, its impact on health-related quality of life (HRQoL) remains significant. In Argentina, no studies have been found that assess HRQoL in this population using locally validated tools. Objective. To assess lung function in children and adolescents with MMC and compare it with that of a healthy control group matched for age and sex.Population and methods. An observational, analytical, cross-sectional study was conducted between December 2023 and December 2024. Patients aged 2 to 18 years were included at a tertiary care hospital. The PedsQL™ 4.0 generic version (proxy-report) questionnaire, validated in Argentina, was used to assess physical, emotional, social, and academic aspects in both sick and healthy children. Results. The study included 68 children with MMC and 68 controls (median age: 9 years). The total PedsQL score was significantly lower in the MMC group compared with the controls (median 65.8 vs. 82.2; p <0.001). The greatest differences were observed in the physical domain (median 56.3 vs. 96.9; p <0.001); emotional functioning showed a smaller difference (median 70 vs. 80; p<0.01). No differences in the HRQoL were observed between patients with or without prenatal surgery, ventriculoperitoneal shunt, or intermittent clean catheterization.Conclusion. The study found that children with MMC have significantly lower HRQoL scores compared to their healthy peers. Introducción. El mielomeningocele (MMC) representa la variante más grave de los defectos del tubo neural, caracterizada por secuelas físicas, cognitivas y sociales. A pesar del desarrollo terapéutico, su impacto en la calidad de vida relacionada a la salud (CVRS) es considerable. En Argentina, no se han encontrado estudios que evalúen la CVRS en esta población utilizando herramientas validadas localmente. Objetivo. Evaluar la CVRS en niños y adolescentes con MMC, y compararla con la de un grupo control sano pareado por edad y sexo. Población y métodos. Estudio observacional, analítico y transversal realizado entre diciembre de 2023 y diciembre de 2024. Se incluyeron pacientes entre 2 y 18 años en un hospital de tercer nivel. Se utilizó el cuestionario PedsQL™ 4.0 versión genérica (proxy-report) validado en Argentina, el cual evalúa aspectos físicos, emocionales, sociales y académicos en niños enfermos o sanos. Resultados. Se incluyeron 68 niños con MMC y 68 controles (edad mediana: 9 años). El puntaje total de la escala PedsQL fue significativamente menor en el grupo MMC frente a los controles (mediana 65,8 vs. 82,2; p <0,001). Las mayores diferencias se observaron en el dominio físico (mediana 56,3 frente a 96,9; p <0,001); el funcionamiento emocional mostró menor diferencia (mediana 70 frente a 80; p <0,01). No se observaron diferencias en la CVRS entre pacientes con o sin cirugía prenatal, derivación ventrículo-peritoneal o cateterismo intermitente limpio. Conclusión.El estudio evidenció que los niños y niñas con MMC presentan una CVRS significativamente inferior en comparación con sus pares sanos.
Leukocyte-stimulating inflammatory cytokines, including interleukin (IL)-27, IL-1β, and IL-10, in conjunction with the transcription factor nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB), are essential in limiting Mycobacterium tuberculosis infections; however, it remains uncertain if these indicators are a reliable indicator of the severity of TB illness. Using real-time polymerase chain reaction (PCR), we examined the mRNA expression of IL-27, IL-1β, IL-10, and NF-κB in peripheral blood mononuclear cell responses in patients with tuberculosis (TB) (n = 25). PCR amplification of 16S specific to mycobacterium DNA showed 84% positivity rate among the 25 samples. Sputum patients with active TB showed higher activation NF-κB mRNA expression when compared to healthy controls. Furthermore, the multidimensional IL-27 secretion in TB patients showed statistically significant mRNA expression as compared to healthy controls. Similarly, TB patients had drastically changed pro-inflammatory cytokine IL-1β mRNA expression. In addition, TB patients' anti-inflammatory cytokine IL-10 mRNA expression was substantially lower than that of healthy controls. Our findings highlight significant alterations in cytokine expression (IL-27, IL-1β, and IL-10) and NF-κB activation in active TB patients, indicating their potential roles in TB pathogenesis. However, further research is required to confirm their value as biomarkers for disease severity. Résumé Contexte:Les cytokines inflammatoires stimulant les leucocytes, notamment l’interleukine (IL)-27, l’IL-1β et l’IL-10, ainsi que le facteur de transcription facteur nucléaire kappa-light-chain-enhancer des cellules B activées (NF-κB), jouent un rôle essentiel dans le contrôle des infections à Mycobacterium tuberculosis. Cependant, leur utilité en tant qu’indicateurs fiables de la gravité de la tuberculose reste incertaine.Matériels et Méthodes:À l’aide de la réaction de polymérisation en chaîne en temps réel (PCR), nous avons analysé l’expression de l’ARNm de l’IL-27, de l’IL-1β, de l’IL-10 et du NF-κB dans les cellules mononucléées du sang périphérique chez des patients atteints de tuberculose (n = 25).Résultat:L’amplification PCR de l’ADN mycobactérien spécifique 16S a montré un taux de positivité de 84 % parmi les échantillons. Les patients atteints de tuberculose active présentaient une expression accrue de l’ARNm du NF-κB par rapport aux témoins sains. De plus, l’expression de l’ARNm de l’IL-27 et de l’IL-1β était significativement augmentée chez les patients atteints de tuberculose, tandis que l’expression de l’IL-10 était significativement réduite.Conclusion:Nos résultats mettent en évidence des altérations importantes de l’expression des cytokines (IL-27, IL-1β et IL-10) et de l’activation du NF-κB chez les patients atteints de tuberculose active, suggérant leur rôle potentiel dans la pathogenèse de la tuberculose.
This study investigates how coworkers' fruit and vegetable consumption and encouragement moderate the association between work-to-family conflict (WTFC) and family-to-work conflict (FTWC) with fruit and vegetable intake among men and women. Using a sample of around 3,200 employees from the European Sustainable Workforce Survey, multilevel linear regression models were used to assess these relationships. WTFC is associated with lower fruit intake among women and vegetable consumption among men; FTWC shows no significant association. Coworkers' fruit intake exacerbates the negative influence of FTWC on fruit intake among men. In contrast, coworkers' encouragement of healthy eating alleviates the negative influence of WTFC and FTWC on women's vegetable intake, and between FTWC and men's fruit intake. Organizations should support employees in managing conflict, maintaining a healthy diet, and establishing a supportive work environment.
Radioactive seed localization (RSL) using 125I is widely employed for the surgical resection of nonpalpable breast lesions due to its precision and scheduling flexibility. Although clinical experience supports its safety, quantifying radiation dose to surrounding healthy breast tissue remains important for establishing conservative operational guidelines, including acceptable implant duration prior to surgery. In this study, cumulative dose to healthy breast tissue from an implanted 125I localization seed was evaluated using two independent computational approaches: a simplified hemispherical breast model implemented in MATLAB and a Monte Carlo simulation developed in Mathematica. Both models incorporated dosimetric parameters from AAPM Task Group 43, including the dose-rate constant, radial dose function, and two-dimensional anisotropy function, along with tissue properties consistent with International Commission on Radiological Protection recommendations. Results from both models demonstrated that cumulative dose decreases rapidly with increasing distance from the seed and increases slowly with implantation time due to the low dose rate and long half-life of 125I. At a distance of 1 cm, cumulative dose reached approximately 3-4 cGy after 5 d and approximately 50 cGy only after extended implantation times exceeding 200 d. Agreement between the MATLAB and Monte Carlo models was within expected limits given differences in deterministic and stochastic modeling approaches. These findings indicate that radiation dose to healthy breast tissue from RSL remains well below thresholds associated with deterministic effects for clinically relevant implantation times. The results support the use of a conservative "no later than" removal date while reaffirming the radiological safety and practical advantages of 125I seed localization in breast cancer surgery.
Sustainable swine production hinges on optimizing sow reproductive efficiency, yet mechanisms driving healthy litter size and weak piglet rates remain unclear. This study categorized sows into high (group H) and low (group L) healthy litter size groups based on median performance. Multi-omics analyses (16S rRNA sequencing, metagenomics, and serum metabolomics) revealed distinct fecal microbiota and metabolic profiles between groups. The results showed significant differences in microbiota composition between groups L and H. Group H exhibited a marked increase in Bacteroidetes abundance (particularly Prevotella sp. CAG1092), concurrent with reduced Firmicutes populations. Metabolomic analysis identified 197 differentially abundant metabolites, with 85 metabolites significantly enriched in group H. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that the differentially abundant metabolites were mainly involved in amino acid synthesis and metabolism, and multiple amino acid metabolic pathways were associated with polyamine synthesis. The correlation results showed a significant correlation (P < 0.05) between these metabolites and litter size as well as litter weight. For instance, Prevotellaceae NK3B31 abundance positively correlated with L-alanine, urea, and securinine, while Prevotella sp. CAG1092 exhibited direct associations with reproductive performance. These findings suggest that gut microbiota dysbiosis may disrupt amino acid homeostasis and polyamine regulation, potentially serving as mechanistic links to reproductive efficiency. Reproductive performance dynamically shapes gut microbiota and systemic metabolism in gestating sows, with litter size influencing fecal metabolite diversity and microbial structure. This integrative analysis establishes a framework for improving both sow productivity and economic viability in pig farming. Optimizing sow reproductive efficiency is vital for sustainable swine production. This study identifies gut microbiota dysbiosis and metabolic imbalances as key drivers of litter size variability. Sows with lower productivity displayed marked reductions in Bacteroidetes (notably Prevotella spp.) and disrupted amino acid/polyamine metabolism, directly linking microbial shifts to poorer litter outcomes. Integrated multi-omics approaches revealed strong correlations between specific taxa (Prevotella sp. CAG1092), metabolites (L-alanine and urea), and reproductive metrics, underscoring the gut-reproductive axis. These findings elucidate mechanistic connections between microbial ecosystems and host physiology, providing a foundation for targeted strategies like microbiota modulation or dietary interventions to enhance metabolic homeostasis and farrowing success. By bridging microbial ecology with livestock productivity, this work advances practical solutions to improve both animal health and agricultural profitability within precision farming frameworks.
Wilson's disease (WD) is a systemic copper toxicity disorder, manifesting as hepatic and neurological symptoms. Sexual health in WD is not well studied. This study aimed to understand sexual health impairment and its related factors in men and women with WD. Men with WD (MeWD) and women with WD (WoWD) were classified as being in the disease-active phase (DAP) or disease maintenance phase (DMP). Disease-related disability was assessed using the Global Assessment Scale for Wilson's Disease (GAS for WD). Sexual health was assessed with the Arizona Sexual Experience Scale (ASEX). Depression and anxiety were assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scales, respectively. Healthy men (MeH) and healthy women (WoH) underwent similar assessments for comparison. The study included 48 MeWD (11 DAP, 37 DMP), 39 WoWD (12 DAP, 27 DMP), 29 MeH, and 34 WoH. In MeWD, ASEX scores (median [Q1-Q3]) were 13 (10-16) in DAP, 13 (11-14) in DMP, and 14 (12-16) in MeH, with no significant differences. However, in WoWD, ASEX scores were more impaired in DAP 19.5 (15.25-24.75) than in DMP 15 (14-17) ( P = 0.029) and WoH 14 (13-18) ( P = 0.025). ASEX scores correlated with GAS for WD in both MeWD ( P = 0.023) and WoWD ( P < 0.001), but not with 24-hour urinary copper excretion at diagnosis. Men and women with WD experience impaired sexual health, which may be related to disease-associated disability. Longitudinal disease registries are required to understand the role of copper metabolism in sexual health impairment in WD.
Traumatic brain injury (TBI) leads to immune dysregulation, which predisposes patients to infections. We hypothesized that TBI leads to poor lung bacterial clearance, due at least in part to dysfunctional neutrophil (PMN) responses. In this study, we characterized both murine and porcine models of TBI plus lung bacterial inoculation to evaluate the effects of TBI on bacterial clearance, and tested the effects of plasma harvested from human TBI patients on PMN function. C57BL6 mice or Yucatan mini swine underwent sham (anesthesia only) or a mild TBI using standardized methods. Four hours later, mice were inoculated with Staphylococcus aureus. Pigs were inoculated with Actinobacter pleuropneumoniae immediately after TBI. At prespecified timepoints after inoculation (24 hr for mice and 72 hr for pigs), animals were euthanized and bronchoalveolar lavage (BAL) and blood were collected, and lung was harvested for further analyses. Plasma from TBI patients was used to perform in vitro assessment of PMN function. C57BL6 mice, Yucatan mini swine, healthy volunteers, and TBI patients. None. In both animal models, TBI predisposed to poor pulmonary bacterial clearance despite significantly increased PMNs in BAL and blood. In vitro, treatment of PMNs with plasma or plasma-derived extracellular vesicles (EVs) from TBI patients led to increased nondirectional chemokinesis, less reactive oxygen species production, and decreased ability to phagocytose. TBI leads to decreased bacterial clearance in the lung in models of TBI + bacterial lung infection, despite increased PMN counts in lung and blood. This is secondary to inappropriate PMN function after TBI, which we demonstrated in vitro via multiple functional assays to be caused, in part, by systemic factors in the plasma, including EVs. Further studies are required to understand the link between TBI and PMN dysfunction that leads to increased susceptibility to bacterial lung infection.
The economic burden that obesity places on society, both directly and indirectly, is considerable. It is acknowledged that obesity is associated with decreased economic productivity; however, the evidence examining the exact relationship between obesity and key metrics of employment in the European context remains to be consolidated. A systematic literature review was performed to determine the association between body mass index (BMI) and employment outcomes. Searches were conducted across three electronic databases (MEDLINE, Embase, and Epistemonikos). Studies were eligible if they were published in or after 2014 and conducted in a European setting. In total, 34 studies were identified; of these, 20 studies provided evidence to show fewer people with obesity were employed as compared to people with overweight or who had a healthy BMI. Obesity was associated with increased sickness absence (n = 7) and impaired work performance (n = 7). Broad evidence collected from across Europe demonstrates that obesity is associated with unemployment, sickness leave, absenteeism, and presenteeism. Preventing and treating obesity would be expected to have a relatively rapid benefit in terms of improved employment outcomes, including productivity, as well as long-term benefits to population health.
Colitis, including necrotizing enterocolitis (NEC), is a common and serious disease in newborns. This study aimed to investigate the specific mechanisms of vitamins A and E in neonatal NEC, given their known roles in inhibiting NF-κB, regulating intestinal flora and reducing inflammatory cytokines. The study measured serum vitamin A and E levels in healthy and NEC newborns/mice. An NEC model was established and mice were treated with vitamins A/E, DDC (SOD/GPx inhibitor), or DDW (SOD/GPx activator). Serum vitamin levels and intestinal inflammatory factors were then assessed. NEC subjects showed significantly lower vitamin A and E levels, which correlated negatively with disease severity. NEC mice exhibited intestinal pathological damage. Vitamin A or E supplementation alleviated this damage and their combination synergistically activated the SOD/GPx pathway, enhancing anti-inflammatory effects. Further inhibition of inflammation and improvement in symptoms were achieved using the SOD/GPx activator DDW. Vitamins A and E may alleviate NEC potentially by modulating inflammatory responses via the SOD/GPx pathway. The correlation between vitamin levels and disease severity suggests a role in intestinal homeostasis, warranting further investigation into microbiota modulation.